Structural Organization of a Full-Length Gp130/LIF-R Cytokine Receptor Transmembrane Complex
Abstract
gp130 is a shared receptor for at least nine cytokines, and can signal either as a homodimer, or as a heterodimer with Leukemia Inhibitory Factor Receptor (LIF-R). Here we biophysically and structurally characterize the full-length, transmembrane form of a quaternary cytokine receptor complex consisting of gp130, LIF-R, the cytokine Ciliary Neurotrophic Factor (CNTF), and its alpha receptor (CNTF-R{alpha}). Thermodynamic analysis indicates that, unlike the cooperative assembly of the symmetric gp130/Interleukin-6/IL-6R{alpha} hexameric complex, CNTF/CNTF-R{alpha} heterodimerizes gp130 and LIF-R via non-cooperative energetics to form an asymmetric 1:1:1:1 complex. Single particle electron microscopic (EM) analysis of the full-length gp130/LIF-R/CNTF-R{alpha}/CNTF quaternary complex elucidates an asymmetric structural arrangement, in which the receptor extracellular and transmembrane segments join as a continuous, rigid unit, poised to sensitively transduce ligand engagement to the membrane-proximal intracellular signaling regions. These studies also enumerate the organizing principles for assembly of the 'tall' class of gp130-family cytokine receptor complexes including LIF, IL-27, IL-12, and others.
- Authors:
- Publication Date:
- Research Org.:
- SLAC National Accelerator Lab., Menlo Park, CA (United States)
- Sponsoring Org.:
- USDOE
- OSTI Identifier:
- 953567
- Report Number(s):
- SLAC-REPRINT-2009-316
Journal ID: ISSN 1097-2765; TRN: US201002%%1395
- DOE Contract Number:
- AC02-76SF00515
- Resource Type:
- Journal Article
- Journal Name:
- Mol. Cell 31:737,2008
- Additional Journal Information:
- Journal Volume: 31; Journal Issue: 5; Journal ID: ISSN 1097-2765
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 60 APPLIED LIFE SCIENCES; COMPLEXES; ELECTRONS; LEUKEMIA; LIGANDS; LYMPHOKINES; PARTICLES; RECEPTORS; SIGNALS; THERMODYNAMICS; Other,OTHER, BIO
Citation Formats
Skiniotis, G, Lupardus, P J, Martick, M, Walz, T, and Garcia, K C. Structural Organization of a Full-Length Gp130/LIF-R Cytokine Receptor Transmembrane Complex. United States: N. p., 2009.
Web.
Skiniotis, G, Lupardus, P J, Martick, M, Walz, T, & Garcia, K C. Structural Organization of a Full-Length Gp130/LIF-R Cytokine Receptor Transmembrane Complex. United States.
Skiniotis, G, Lupardus, P J, Martick, M, Walz, T, and Garcia, K C. 2009.
"Structural Organization of a Full-Length Gp130/LIF-R Cytokine Receptor Transmembrane Complex". United States.
@article{osti_953567,
title = {Structural Organization of a Full-Length Gp130/LIF-R Cytokine Receptor Transmembrane Complex},
author = {Skiniotis, G and Lupardus, P J and Martick, M and Walz, T and Garcia, K C},
abstractNote = {gp130 is a shared receptor for at least nine cytokines, and can signal either as a homodimer, or as a heterodimer with Leukemia Inhibitory Factor Receptor (LIF-R). Here we biophysically and structurally characterize the full-length, transmembrane form of a quaternary cytokine receptor complex consisting of gp130, LIF-R, the cytokine Ciliary Neurotrophic Factor (CNTF), and its alpha receptor (CNTF-R{alpha}). Thermodynamic analysis indicates that, unlike the cooperative assembly of the symmetric gp130/Interleukin-6/IL-6R{alpha} hexameric complex, CNTF/CNTF-R{alpha} heterodimerizes gp130 and LIF-R via non-cooperative energetics to form an asymmetric 1:1:1:1 complex. Single particle electron microscopic (EM) analysis of the full-length gp130/LIF-R/CNTF-R{alpha}/CNTF quaternary complex elucidates an asymmetric structural arrangement, in which the receptor extracellular and transmembrane segments join as a continuous, rigid unit, poised to sensitively transduce ligand engagement to the membrane-proximal intracellular signaling regions. These studies also enumerate the organizing principles for assembly of the 'tall' class of gp130-family cytokine receptor complexes including LIF, IL-27, IL-12, and others.},
doi = {},
url = {https://www.osti.gov/biblio/953567},
journal = {Mol. Cell 31:737,2008},
issn = {1097-2765},
number = 5,
volume = 31,
place = {United States},
year = {Tue May 26 00:00:00 EDT 2009},
month = {Tue May 26 00:00:00 EDT 2009}
}